The Effect of Anti-Solvents on Protein Solubility

Another common chemical additive utilized to reduce protein solubility is small, polar organic molecules such as methanol, ethanol, and acetone. Such water-miscible solvents are often called anti-solvents. The most widely known separation utilizing such solvents is the Cohn method of blood fractionation, which utilizes ethanol for the recovery of a variety of proteins from blood (Cohn et al. 1940). Such separations are usually carried out near the isoelectric point in order to bring the protein to a point of minimal solubility and minimize the amount of anti-solvent required to achieve the precipitation or crystallization. 

Although a reasonable model, the real source of reduced solubility is more complicated than a simple dielectric constant reduction as 

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